Xihui
Zhao

DUIRI Pre-differentiation short-chain PFAS exposure induce neurotoxicity via altering ER vulnerability in dopaminergic-like neurons

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Authors:

Xihui Zhao

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Per- and polyfluorinated alkyl substances (PFAS) are a large group of surface-active compounds, which are commonly used in industrial processes and everyday consumer products, affecting the majority of the population. The adverse health effects associated with conventional long-chain PFAS, include increased risks of cancer immune system dysfunction, and neurodegenerative diseases, which collectively led to the replacement of long-chain PFAS such as PFOA and PFOS with short-chain alternatives such as PFBA and PFBS. The health implications of short-chain PFAS, particularly neurotoxicity, however, remains understudied posing long-term health risk in the exposed population. In this study, we exposed progenitor like cells, SH- SY5Y, to 0.4 and 4 μg/L of PFBS or PFBA for four days. We then removed the PFAS upon the onset of differentiation. After 14 day differentiation, we characterized neuronal network and assessed the intensity of tyrosine hydroxylase (TH). Altered TH intensity was observed after prior exposure to short-chain PFBA or PFBS. In addition, chemicals known to target mitochondria (MPP+) and endoplasmic reticulum (ER) (Tunicamycin) were used to test vulnerability after developmental PFBA or PFBS exposure. Our results revealed that cells previously exposed to PFBA exhibited modified sensitivity to ER stimulation. We also assessed changes in epigenetic markers to understand the potential molecular targets contributing to the establishment of a persistent neurotoxic state in DA-like neurons after prior PFBA or PFBS exposure. Collectively, our results identified neurotoxicity of low-dose PFBA or PFBS exposure in human DA-like neurons following a developmental exposure scheme.

Source:

Purdue University / 2023

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Co-authors:

Xihui Zhao

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